1-(4-(hexyloxy)phenyl)-3-methylbutan-1-one | 1162128-85-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-(hexyloxy)phenyl)-3-methylbutan-1-one
• 英文别名: 1-(4-Hexoxyphenyl)-3-methylbutan-1-one；1-(4-hexoxyphenyl)-3-methylbutan-1-one
• CAS: 1162128-85-9
• 化学式: C₁₇H₂₆O₂
• 分子量: 262.392
• InChiKey: VMQWVUKXKHEXRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 1-(4-(hexyloxy)phenyl)-3-methylbutan-1-one 、 盐酸二甲胺 在 盐酸 作用下， 以 水 、 乙腈 为溶剂， 反应 2.0h， 以50%的产率得到2-((dimethylamino)methyl)-1-(4-(hexyloxy)phenyl)-3-methylbutan-1-one
  参考文献：
  名称：

  Improvement of Pharmacological Properties of Irreversible Thyroid Receptor Coactivator Binding Inhibitors

  摘要：

  We have previously reported the discover), and preliminary structure activity relationships of a series of beta-aminoketones that disrupt the binding of coactivators to TR. However, the most active compounds had moderate inhibitory potency and relatively high cytotoxicity, resulting in narrow therapeutic index. Additionally, preliminary evaluation of in vivo toxicology revealed a significant dose related cardiotoxicity. Here we describe the improvement of pharmacological properties of thyroid hormone receptor coactivator binding inhibitors. A comprehensive Survey of the effects of substitutents in key areas of the molecule was carried out based on mechanistic insight from the earlier report. This study revealed that both electron withdrawing and hydrophobic substituents on the aromatic ring led to higher potency. On the other hand, moving from an alkyl to a sulfonyl alkyl side chain led to reduced cytotoxicity, Finally, utilization of airline moieties having low pK(a)'s resulted in lowered ion channel activity without any loss of pharmacological activity.

  DOI：

  10.1021/jm9002704
• 作为产物：
  描述：

  溴己烷 、 1-(4-羟基苯基)-3-甲基丁烷-1-酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以75%的产率得到1-(4-(hexyloxy)phenyl)-3-methylbutan-1-one
  参考文献：
  名称：

  Improvement of Pharmacological Properties of Irreversible Thyroid Receptor Coactivator Binding Inhibitors

  摘要：

  We have previously reported the discover), and preliminary structure activity relationships of a series of beta-aminoketones that disrupt the binding of coactivators to TR. However, the most active compounds had moderate inhibitory potency and relatively high cytotoxicity, resulting in narrow therapeutic index. Additionally, preliminary evaluation of in vivo toxicology revealed a significant dose related cardiotoxicity. Here we describe the improvement of pharmacological properties of thyroid hormone receptor coactivator binding inhibitors. A comprehensive Survey of the effects of substitutents in key areas of the molecule was carried out based on mechanistic insight from the earlier report. This study revealed that both electron withdrawing and hydrophobic substituents on the aromatic ring led to higher potency. On the other hand, moving from an alkyl to a sulfonyl alkyl side chain led to reduced cytotoxicity, Finally, utilization of airline moieties having low pK(a)'s resulted in lowered ion channel activity without any loss of pharmacological activity.

  DOI：

  10.1021/jm9002704

文献信息

• Improvement of Pharmacological Properties of Irreversible Thyroid Receptor Coactivator Binding Inhibitors
  作者：Jong Yeon Hwang、Leggy A. Arnold、Fangyi Zhu、Aaron Kosinski、Thomas J. Mangano、Vincent Setola、Bryan L. Roth、R. Kiplin Guy

  DOI：10.1021/jm9002704

  日期：2009.7.9

  We have previously reported the discover), and preliminary structure activity relationships of a series of beta-aminoketones that disrupt the binding of coactivators to TR. However, the most active compounds had moderate inhibitory potency and relatively high cytotoxicity, resulting in narrow therapeutic index. Additionally, preliminary evaluation of in vivo toxicology revealed a significant dose related cardiotoxicity. Here we describe the improvement of pharmacological properties of thyroid hormone receptor coactivator binding inhibitors. A comprehensive Survey of the effects of substitutents in key areas of the molecule was carried out based on mechanistic insight from the earlier report. This study revealed that both electron withdrawing and hydrophobic substituents on the aromatic ring led to higher potency. On the other hand, moving from an alkyl to a sulfonyl alkyl side chain led to reduced cytotoxicity, Finally, utilization of airline moieties having low pK(a)'s resulted in lowered ion channel activity without any loss of pharmacological activity.